Diseases of the pulmonary vascular bed including pulmonary hypertension are important national health problems. However, effective treatment for many of these diseases is not available at the present time. The inadequacy of treatment of these diseases may be due in part to a lack of fundamental knowledge concerning structure, ultrastructure, physiology and pharmacology of of pulmonary vessels. In addition, an animal model for pulmonary hypertension is needed so that the progression and course of the disease can be followed and new forms of therapy evaluated. The lung is well supplied with both adrenergic and cholinergic nerves and with the possible exception of the kidney is unsurpassed in its ability to synthesize, release, activate and biotransform hormonal substances. A major goal of the proposed study is to broaden our knowledge of the structure and of the control of the pulmonary circulation by neural and endocrine factors with particular emphasis on the prostaglandins. In addition to fundamental studies on nervous and endocrine factors in the lung a second major goal is to develop an animal model for pulmonary hypertension and evaluate new modes of therapy. In contrast to the lung, it is well established that vascular tone in the peripheral vascular bed is controlled by the adrenergic nervous system and it has become apparent recently that prostaglandins possess the ability to regulate the activity of the adrenergic system. A third major goal of the proposed study is to define the action of the prostaglandins on the peripheral vascular bed. Thus, the effects of the prostaglandins on vascular resistance and vasomotor responses to sympathetic stimulation, pressor and depressor hormones will be investigated in the renal, intestinal and hindlimb vascular beds. The proposed experiments will provide important information on possible pro and anti-hypertensive actions of the prostaglandins. In addition, the role of the prostaglandins in regulating excretory function will be analyzed in the in situ perfused kidney under conditions of controlled blood flow.